Two Tamiflu-resistant swine flu cases reported in Washington

[HenryN]

Two Tamiflu-resistant swine flu cases reported in WA


03:19 PM PDT on Friday, August 14, 2009


KING5.com

SEATTLE – The health department says two immunosuppressed patients being treated for swine flu in King County have been identified as resistant to Tamiflu, an antiviral treatment.
The patients include a male teenager and a female in her 40s who have no links to each other.
The health department says both patients had compromised immune systems, which has been shown to raise the risk for prolonged infection and development of antiviral resistance.
One patient has recovered and the other is being treated with a different antiviral medication.
Health officials say there is no evidence indicating that people who came in contact with the two patients became infected with a Tamiflu-resistant virus.
Officials say Tamiflu resistance remains rare. As of Aug. 11, health officials have identified a total of 11 novel H1N1 flu viruses that are resistant to Tamiflu worldwide.
"Viruses can develop drug resistance over time. It's important that antiviral treatments only be used as recommended by a health care provider, to minimize drug resistance and preserve an important tool against the illness for those who need it," said Dr. David Fleming, Director and Health Officer for Public Health - Seattle & King County. "The vast majority of people with H1N1 virus continue to be treatable with Tamiflu, and in cases where it becomes ineffective, other options are available."

[HenryN]

Two locally-treated patients infected with Tamiflu-resistant H1N1 virus (swine flu)

Friday, August 14, 2009 Tamiflu resistance remains rare; monitoring ongoing

KING COUNTY, WA - In a report that is planned for publication today in the federal Centers for Disease Control and Prevention's Morbidity and Mortality Weekly Report Dispatch, two immunosuppressed patients being treated for H1N1 (swine flu) influenza in King County have been identified as resistant to oseltamivir, commonly known by the brand name Tamiflu, an antiviral treatment used for the infection.
"Viruses can develop drug resistance over time. It's important that antiviral treatments only be used as recommended by a health care provider, to minimize drug resistance and preserve an important tool against the illness for those who need it," said Dr. David Fleming, Director and Health Officer for Public Health - Seattle & King County. "The vast majority of people with H1N1 virus continue to be treatable with Tamiflu, and in cases where it becomes ineffective, other options are available."
Currently, antiviral drug treatment for H1N1 virus infections with oseltamivir or zanamivir (Relenza) is recommended for hospitalized persons who are ill with influenza and outpatients who are at high risk of complications, including young children, pregnant women, and persons with chronic medical conditions such as lung disease, asthma, heart disease and diabetes. No changes in antiviral treatment recommendations have been made as a result of these two cases.
The two patients, one a male teenager and the other a female in her 40's, had no links to one another and these infections are not believed to be related. Both patients had compromised immune systems, a condition that has previously been shown to raise the risk for prolonged seasonal influenza virus infection and development of antiviral resistance during treatment. One patient is currently no longer ill from the influenza virus infection and the other has ongoing symptoms and is being treated with the antiviral medication zanamivir. More details about the cases will be found in the MMWR Dispatch at www.cdc.gov/mmwr.
There is no evidence that health care workers or other contacts of these two people became infected with a Tamiflu-resistant virus. The risk of infection to the general population is very low from these cases, but as a precaution, local and state health officials are working in collaboration with the CDC to conduct enhanced monitoring for antiviral drug resistant influenza in the community.
As of August 11, 2009, a total of 11 novel H1N1 influenza viruses that are resistant to Tamiflu have been reported worldwide.
A vaccine for the H1N1 virus is being developed rapidly in anticipation of a resurgence of the H1N1 virus in the United States this fall. Locally, Public Health is preparing to distribute vaccine in the most effective way to those recommended to receive it as it becomes available. Federal officials are reporting that current plans are to begin delivering vaccine in October.
Check Public Health's website for frequently updated information and resources: www.kingcounty.gov/health/H1N1.

http://www.kingcounty.gov/healthserv.../09081401.aspx

[HenryN]

August 14, 2009 / 58 (Dispatch);1-4

Oseltamivir-Resistant Novel Influenza A (H1N1) Virus Infection in Two Immunosuppressed Patients --- Seattle, Washington, 2009 Novel influenza A (H1N1) virus infection continues to cause illness and death among persons worldwide. Immunosuppressed patients with influenza virus infection can shed virus for prolonged periods, increasing the chances for development of drug resistance (1--3). On August 6, 2009, CDC detected evidence of resistance to the antiviral medication oseltamivir in two severely immunosuppressed patients with novel influenza A (H1N1) virus infection in Seattle, Washington. The two patients were treated in two different hospitals, and their cases were not epidemiologically linked. Both were being treated with oseltamivir for novel influenza A (H1N1) virus infection and had prolonged viral shedding. In both patients, the virus was documented as initially susceptible to oseltamivir, and resistance developed subsequently during treatment with the drug. Testing of viral RNA from both patients by pyrosequencing detected a mutation that results in a histidine-to-tyrosine substitution at position 275 (H275Y) in the neuraminidase, known to be associated with oseltamivir resistance (4,5). The results were confirmed by pyrosequencing, sequencing of the neuraminidase gene, and neuraminidase inhibition testing of virus isolates on August 11. One patient's symptoms resolved after treatment with oseltamivir, and the other patient was receiving treatment with zanamivir and ribavirin as of August 13. An investigation of health-care personnel (HCP) contacts and other close contacts revealed no evidence of virus transmission. This report summarizes the case histories and resulting investigations and highlights the importance of 1) close monitoring for antiviral drug resistance among immunosuppressed patients receiving treatment for novel influenza A (H1N1) virus infection and 2) the implications for infection control. Case Reports Case 1. A teen-aged male was diagnosed with leukemia in November 2008 and subsequently received outpatient immunosuppressive chemotherapy. On April 29, 2009, he was hospitalized for a hematopoietic stem cell transplant, which he received on May 7. He received immunosuppressive treatment prior to his transplantation and remained hospitalized in a single-patient room after the transplantation. On May 31, he developed fever, mild cough, and rhinorrhea, was placed on droplet and contact precautions, and HCP began using respirators (fit-tested N95 or higher-level protection) for his care. A nasal wash specimen collected on May 31 tested positive for novel influenza A (H1N1) virus by real-time reverse transcription--polymerase chain reaction (rRT-PCR) at the University of Washington Virology Laboratory. On June 1, the patient was enrolled in an influenza antiviral treatment study and he began a 10-day course of oseltamivir. However, on June 4, novel influenza A (H1N1) virus was detected again by rRT-PCR and viral culture in nasal wash specimens, and oseltamivir treatment was extended to a 20-day course, to June 20. The patient improved and was discharged to a nearby apartment on June 7. Virus again was detected in nasal wash specimens on June 11. On July 7, a nasal wash specimen collected for routine follow-up on an outpatient basis was positive for novel influenza A (H1N1) virus by rRT-PCR; oseltamivir therapy was resumed on July 8. The patient remained well until July 14, when he was hospitalized with fever and treated for coagulase-negative staphylococcal infection of an indwelling central venous catheter. A nasal wash specimen collected on July 14 tested positive for novel influenza A (H1N1) virus by rRT-PCR, and his oseltamivir was increased to a high dose, 150 mg orally, twice a day. Increased rhinorrhea and mild cough were noted on July 16. The patient was discharged on oseltamivir on July 18. Because of prolonged shedding of novel influenza A (H1N1) virus and suspected oseltamivir resistance, nasal wash specimens previously collected from the patient were sent to CDC for antiviral resistance testing and arrived on August 5. On August 6, pyrosequencing at CDC of viral RNA from a specimen collected on June 4 revealed susceptibility to oseltamivir. However, pyrosequencing of a follow-up specimen collected on July 30 indicated oseltamivir resistance, based on detection of the H275Y mutation (4,5). Treatment of the patient with oseltamivir was stopped on August 6, when CDC pyrosequencing results from the specimens became available. Because the patient was asymptomatic, no further treatment was indicated. On August 10, CDC received previously collected virus isolates from the patient for pyrosequencing on August 11, which confirmed the previous results. A novel influenza A (H1N1) virus isolate from a specimen collected on May 31 was identified as susceptible to oseltamivir by pyrosequencing at CDC, but viruses isolated from specimens collected on June 11 and July 14 had the H275Y mutation, indicating oseltamivir resistance. Seattle-King County health department investigators interviewed hospital infection-control staff and the patient's family members and visitors. Surveillance for influenza-like illness (ILI) among staff members is standard policy at the hospital where the patient was treated. No cases of ILI were reported among approximately 100 HCP contacts of the patient. Active surveillance, involving personal interviews of HCP contacts during the 2 weeks before diagnosis of oseltamivir resistance did not identify any HCP with ILI. After each hospital discharge, the patient lived under voluntary home isolation according to standard protocol for patients in the post-hematopoietic stem cell transplant (HSCT) period; he did not attend any school. When traveling in public, the patient reported wearing a surgical mask per protocol for immunosuppressed HCST recipients and avoiding close contact with other persons and crowds. None of the 12 family member contacts or other persons who had visited the patient while he was in isolation reported symptoms of ILI. Case 2: A female patient in her 40s who had a hematopoietic stem cell transplant for leukemia had a recurrence of leukemia in December 2008. She underwent two cycles of immunosuppressive chemotherapy during March--April 2009. On June 21, she was admitted to the hospital for further chemotherapy; she also had developed a fever and symptoms of an upper respiratory infection. She was placed in a single-patient room with droplet and contact precautions, and a nasal wash specimen was obtained for direct fluorescent antibody staining (DFA) and viral culture. The DFA result was indeterminate because of an inadequate cellular specimen; however, on June 26, the University of Washington Virology Laboratory reported isolation of influenza A virus from the specimen. Antiviral treatment with high-dose oseltamivir (150 mg orally, twice a day) and rimantadine (100 mg orally, twice a day) was administered during June 26--July 1. On July 3, the viral isolate was identified as novel influenza A (H1N1), and high-dose oseltamivir and rimantadine were restarted. The patient's respiratory status worsened, and she required supplemental oxygen for hypoxia. Novel influenza A (H1N1) virus was isolated from additional nasal wash specimens collected on July 6 and July 14, and from bronchoalveolar lavage specimens obtained on July 16 and 28. Because of prolonged viral shedding, specimens were sent to CDC on August 4 for antiviral susceptibility testing. Treatment with inhaled zanamivir was attempted, but was poorly tolerated, and oseltamivir was continued. On August 6, CDC determined that pyrosequencing of viral RNA from the first clinical specimen collected on June 21 did not detect the H275Y mutation. However, the mutation was detected by pyrosequencing of viral RNA from a nasal wash specimen collected on July 28. Treatment of the patient with oseltamivir was discontinued when results became available. Treatment with inhaled zanamivir after identification of oseltamivir resistance again was attempted but poorly tolerated. On August 7, intravenous zanamivir, acquired through an emergency investigational new drug application for compassionate use, and aerosolized ribavirin therapy were initiated. As of August 13, the patient remained symptomatic and hospitalized on intravenous zanamivir and had been switched to oral ribavirin because of intolerance of aerosolized ribavirin. The patient's hospital course was complicated by prolonged neutropenia and protracted bone marrow recovery, neutropenic fever, coagulase-negative Staphylococcus bacteremia, and Pneumocystis jirovecii pneumonia. On August 10, CDC received other previously collected virus isolates from this patient for testing, and pyrosequencing of a virus isolated from a specimen collected on July 14 had the H275Y mutation, confirming oseltamivir resistance. The patient was hospitalized in a single-patient room upon admission on June 21. She was initially placed on droplet and contact precautions. Immediately after confirmation of novel influenza A (H1N1) virus infection, use of N95 repirators by HCP also was implemented. Active surveillance for respiratory illness among staff members is routine at the hospital where the patient was treated, and no cases of ILI or other acute respiratory illness were reported among the approximately 200 HCP contacts who cared for the patient. No breaches of personal protective equipment recommendations (including use of fit-tested N-95 respirators) were reported among HCP contacts caring for this patient. Testing of Clinical Specimens for Oseltamivir Resistance CDC has tested virus isolates or clinical specimens collected from 37 additional Washington residents with confirmed novel influenza A (H1N1) virus infection during April 26--July 30. None of these viruses had evidence of the H275Y mutation. As of August 11, of the 670 novel influenza A (H1N1) viruses collected since April 2009 in the United States and tested at CDC, 318 had been tested for oseltamivir and zanamivir resistance by neuraminidase inhibition assay, and 352 clinical specimens had been screened for oseltamivir resistance for the H275Y mutation by pyrosequencing. No other oseltamivir-resistant viruses had been identified. Oseltamivir-resistant viruses isolated from both patients described in this report were determined to be susceptible to zanamivir by neuraminidase inhibition assay at CDC. Sequence analysis of the neuraminidase gene of these oseltamivir-resistant viruses showed that oseltamivir resistance was not the result of gene reassortment with seasonal influenza A (H1N1) virus. Reported by: J Englund, MD, D Zerr, MD, J Heath, Seattle Children's Hospital, Univ of Washington, and Fred Hutchinson Cancer Research Center; S Pergam, MD, J Kuypers, PhD, J Yager, MD, M Boeckh, MD, D Mattson, N Whittington, E Whimbey, MD, Univ of Washington Medical Center and Fred Hutchinson Cancer Research Center; J Duchin, MD, Public Health --- Seattle & King County, Washington. T Uyeki, MD, V Deyde, PhD, M Okomo-Adhiambo, PhD, T Sheu, A Trujillo, A Klimov, PhD, ScD, L Gubareva, MD, PhD, Influenza Div, National Center for Immunization and Respiratory Diseases; M Kay, DVM, EIS Officer, CDC. Editorial Note: This report describes oseltamivir-resistant novel influenza A (H1N1) virus infection in two severely immunosuppressed patients who were treated with oseltamivir for acute illness symptoms of laboratory-confirmed influenza. Initially, both patients were infected with oseltamivir-susceptible viruses; oseltamivir resistance developed later during antiviral treatment. The two patients were not epidemiologically linked and were treated at different hospitals. No evidence was found that HCP or other patient contacts developed ILI caused by oseltamivir-resistant novel influenza A (H1N1) virus infection. Immunosuppressed patients are at increased risk for complications of influenza and are recommended for annual influenza vaccination, although the immune response to vaccination can be decreased in some persons (6,7). In otherwise healthy adults with seasonal influenza virus infection, viral shedding generally resolves within 7 days, compared with immunosuppressed patients, who can experience prolonged viral shedding for weeks to months. Antiviral resistance can develop during treatment of influenza in these patients, and prolonged viral shedding (1,2) of up to 18 months has been reported, including shedding of oseltamivir-resistant seasonal influenza A virus for more than 1 year (3). Clinicians caring for immunosuppressed patients with novel influenza A (H1N1) virus infection should be aware of the potential for development of antiviral drug resistance during therapy and prolonged viral shedding. Recommendations for prevention and control of seasonal influenza among hematopoietic stem cell transplant recipients, their family members, and HCP have been published (8). Strict adherence to recommended personal protective equipment and infection-control measures is advised until an immunosuppressed patient with influenza virus infection has serial respiratory specimens that remain negative when tested by both rRT-PCR and viral culture. Interim infection-control guidance for novel influenza A (H1N1) is available on the CDC website.* Only sporadic cases of oseltamivir resistance associated with the H275Y mutation in the neuraminidase have been detected in immunocompetent persons exposed to oseltamivir (9). As of August 11, no evidence had been found of ongoing transmission of oseltamivir-resistant novel influenza A (H1N1) virus in the United States or elsewhere in the world. The public health risk of virus transmission from these two immunosuppressed cases with oseltamivir-resistant novel influenza A (H1N1) virus infection appears to be low. Currently, enhanced surveillance for oseltamivir resistance among novel influenza A (H1N1) virus strains isolated from outpatients and hospitalized patients is being conducted in Washington in collaboration with CDC. The two cases in immunosuppressed patients described in this report and sporadic cases of oseltamivir resistance in persons with oseltamivir exposure, highlight the need for ongoing global virologic surveillance and monitoring of antiviral resistance (10). All circulating novel influenza A (H1N1) virus strains worldwide remain susceptible to oseltamivir and zanamivir but resistant to amantadine and rimantadine. CDC continues to recommend oseltamivir or zanamivir for treatment of all hospitalized patients with suspected or confirmed novel influenza A (H1N1) virus infection and for outpatients at increased risk for influenza-related complications (e.g., young children, pregnant women, and persons with certain chronic medical conditions) with suspected or confirmed novel influenza A (H1N1) virus infection. Novel influenza A (H1N1) virus strains with the H275Y mutation are susceptible to zanamivir. Therefore, in immunosuppressed patients with oseltamivir-resistant novel A (H1N1) virus infection, zanamivir should be considered the antiviral treatment of choice; however, zanamivir is not recommended for persons with underlying airway disease.† Additional interim guidance on the use of antiviral medications for the treatment and prevention of novel influenza A (H1N1) virus infection is available on the CDC website.§ References Klimov AI, Rocha E, Hayden FG, Shult PA, Roumillat LF, Cox NJ. Prolonged shedding of amantadine-resistant influenzae A viruses by immunodeficient patients: detection by polymerase chain reaction-restriction analysis. J Infect Dis 1995;172:1352--5. Ison MG, Gubareva LV, Atmar RL, Treanor J, Hayden FG. Recovery of drug-resistant influenza virus from immunocompromised patients: a case series. J Infect Dis 2006;193:760--4. Weinstock DM, Gubareva LV, Zuccotti G. Prolonged shedding of multidrug-resistant influenza A virus in an immunocompromised patient. N Engl J Med 2003;27;348:867--8. Deyde VM, Gubareva LV. Influenza genome analysis using pyrosequencing method: current applications for a moving target. Expert Rev Mol Diagn 2009;9:493--509. World Health Organization. CDC pyrosequencing assay to detect H275Y mutation in the neuraminidase of novel A (H1N1) viruses. Available at http://www.who.int/csr/resources/publications/swineflu/NA_DetailedPyrosequencing_20090513.pdf. CDC. Prevention and control of seasonal influenza with vaccines: recommendations of the Advisory Committee on Immunization Practices (ACIP), 2009. MMWR 2009;58(No. RR-8). Kunisaki KM, Janoff EN. Influenza in immunosuppressed populations: a review of infection frequency, morbidity, mortality, and vaccine responses. Lancet Infect Dis 2009;9:493--504. CDC. Guidelines for preventing opportunistic infections among hematopoietic stem cell transplant recipients: recommendations of CDC, the Infectious Disease Society of America, and the American Society of Blood and Marrow Transplantation. MMWR 2000(No. RR-10). World Health Organization. Pandemic (H1N1) 2009. Update 60. Laboratory-confirmed cases of pandemic (H1N1) 2009 as officially reported to WHO by states parties to the IHR (2005) as 31 July 2009. Available at http://www.who.int/csr/don/2009_08_04/en/index.html. Sheu TG, Deyde VM, Okomo-Adhiambo M, et al. Surveillance for neuraminidase inhibitor resistance among human influenza A and B viruses circulating worldwide in 2004--2008. Antimicrob Agents Chemother 2008;52:3284--92. * Available at http://www.cdc.gov/h1n1flu/guidelines_infection_control.htm. † Available at http://us.gsk.com/products/assets/us_relenza.pdf. § Available at http://www.cdc.gov/h1n1flu/recommendations.htm. http://www.cdc.gov/mmwr/preview/mmwr...m58d0814a1.htm

[HenryN]

US swine flu patients on immunosuppressant drugs develop Tamiflu resistance
By Helen Branswell (CP) – 1 hour ago
Two cases of Tamiflu-resistant swine flu have been found in the United States, in leukemia patients who were immunosuppressed, the U.S. Centers for Disease Control said in a report due to be published late Friday.
The cases have greater implications than did earlier sporadic findings of Tamiflu-resistant pandemic flu viruses, experts say.
And they highlight the catch-22 of treating pandemic influenza in people who are immunosuppressed. These patients should be given flu drugs because their immune status leaves them highly vulnerable to severe illness. But giving them the drugs raises at least the theoretical risk that they will develop and spread antiviral resistant strains of the novel H1N1 flu.
"That's a legitimate public health concern," said Dr. Frederick Hayden, an antiviral expert at the University of Virginia.
It's well known that people with suppressed immune systems - either from birth, disease or because they are taking anti-rejection drugs following transplant surgery - can have prolonged viral replication when they get infected with influenza.
Studies suggest such patients can shed viruses for weeks and even months after a bout of flu.
If they are taking antiviral drugs, the longer they shed viruses, the more likely they are to develop resistance to the drugs. And if they develop drug resistance, they could - at least in theory - transmit those resistant viruses to others.
An influenza expert with the CDC said given what's known about flu in immunosuppressed patients, officials have been expecting to see cases of resistance to oseltamivir (Tamiflu's generic name) in this patient population.
"It's not a surprise that this has occurred in immunosuppressed patients treated with oseltamivir," Dr. Tim Uyeki said in an interview from Atlanta.
"And it is important for clinicians, family members, caregivers to be aware ... that there is potential for prolonged viral shedding and antiviral resistance to develop in patients with novel H1N1 virus infection."
Health-care workers and contacts of the two patients have been investigated and there is currently no evidence either patient transmitted Tamiflu-resistant viruses to others, Uyeki said.
Both cases occurred in Seattle, though it is believed there is no link between the two. Both - a teenaged male and a woman in her 40s - have leukemia and both had previously undergone stem cell transplants for their cancer.
The teenager has recovered but the woman remains in hospital receiving a different flu drug, Relenza and another antiviral drug, ribavirin.
Uyeki said the CDC isn't changing its recommendations on antiviral treatment as a consequence of the findings.
The agency recommends people who contract pandemic influenza be treated with either Tamiflu or Relenza if they are hospitalized or if they are at high risk of becoming seriously ill because they are pregnant or have a disease known to complicate recovery from flu.
But Uyeki said if there is evidence of Tamiflu resistance or even if it is suspected because the patient isn't recovering, Relenza should be used.
Since the pandemic began, 11 cases of Tamiflu resistance have been reported. Three cases apiece have been found in Japan and China - one on the mainland in Hunan province and two in Hong Kong. Canada, Denmark and Singapore have each found one.
Most of these cases have occurred in people who took the drug as treatment for swine flu or to prevent infection with swine flu.
The sole exception so far is the one of the cases reported by Hong Kong, which was in a teenager who travelled from the United States. She had not previously taken Tamiflu, suggesting she was infected from the start with a resistant virus. The source of her infection was not found and no other cases of resistance have been reported from the San Francisco area, where she lives.

Follow Canadian Press Medical Writer Helen Branswell's flu updates on Twitter at CP-Branswell

http://www.google.com/hostednews/can...0p8MsxNzEVCjkg

[HenryN]

Two Tamiflu-resistant swine flu cases reported in WA


03:33 PM PDT on Friday, August 14, 2009


KING5.com

SEATTLE – The health department says two immunosuppressed patients being treated for swine flu in King County have been identified as resistant to Tamiflu, an antiviral treatment.
The patients include a male teenager and a female in her 40s who have no links to each other.
The health department says both patients had compromised immune systems, which has been shown to raise the risk for prolonged infection and development of antiviral resistance.
One patient has recovered and the other is being treated with a different antiviral medication.
Health officials say there is no evidence indicating that people who came in contact with the two patients became infected with a Tamiflu-resistant virus.
Officials say Tamiflu resistance remains rare. As of Aug. 11, health officials have identified a total of 11 novel H1N1 flu viruses that are resistant to Tamiflu worldwide.
"Viruses can develop drug resistance over time. It's important that antiviral treatments only be used as recommended by a health care provider, to minimize drug resistance and preserve an important tool against the illness for those who need it," said Dr. David Fleming, Director and Health Officer for Public Health - Seattle & King County. "The vast majority of people with H1N1 virus continue to be treatable with Tamiflu, and in cases where it becomes ineffective, other options are available."

http://www.nwcn.com/topstories/stori....de2089a7.html

[Rwilmer]

Obviously tamiflu is out as a treatment option at this point in time, unfortunately.

[HenryN]

Originally Posted by Rwilmer

Obviously tamiflu is out as a treatment option at this point in time, unfortunately.

These two cases are somewhat of a special case because they were immunosupressed, and therefore can't easily clear the virus. Consequently, they remain infected over a long time period, which leads to even lower levels of H274Y bubbling ot the surface or allows for the selection of de novo mutations. However, the fact that both cases with in Kings County, WA leads to concerns of a connection, which could be addressed to some degree by release of the sequences.

[Mamabird]

And the beat goes on, and the beat goes on, on, on, on.

[mixin]

Sequence analysis of the neuraminidase gene of these oseltamivir-resistant viruses showed that oseltamivir resistance was not the result of gene reassortment with seasonal influenza A (H1N1) virus.

This is a good thing, isn't it?

[Mamabird]

Originally Posted by mixin

This is a good thing, isn't it?

Yes.

Even though Tamiflu resistance is Tamiflu resistance irrespective of how acquired, reassortment with a new NA segment would mean an antigenic novel Swine Flu virus. In other words, the vaccines being developed around CA/07 would likely be much less effective against such a pathogen.

[HenryN]

Originally Posted by mixin

This is a good thing, isn't it?

No. Its nonsense. Acquiring H and N from human wouldn't create a pandemic strain.

[HenryN]

Originally Posted by Mamabird

Yes.

Even though Tamiflu resistance is Tamiflu resistance irrespective of how acquired, reassortment with a new NA segment would mean an antigenic novel Swine Flu virus. In other words, the vaccines being developed around CA/07 would likely be much less effective against such a pathogen.

Wrong. The acquiring a Brisbane/59 H and N would produce a strain similar to seasonal H1N1 (population would already have antibodies). Its hopes and dreams on steroid.
It has already happened in Saskatchewan with another triple reassortant.

[HenryN]

Commentary

[AlaskaDenise]

Originally Posted by niman

Commentary

Commentary

Tamiflu Resistant Pandemic H1N1 in Washington State

Recombinomics Commentary 03:20
August 15, 2009


On June 1, the patient was enrolled in an influenza antiviral treatment study and he began a 10-day course of oseltamivir.

A novel influenza A (H1N1) virus isolate from a specimen collected on May 31 was identified as susceptible to oseltamivir by pyrosequencing at CDC, but viruses isolated from specimens collected on June 11 and July 14 had the H275Y mutation, indicating oseltamivir resistance.

Antiviral treatment with high-dose oseltamivir (150 mg orally, twice a day) and rimantadine (100 mg orally, twice a day) was administered during June 26--July 1.

On August 10, CDC received other previously collected virus isolates from this patient for testing, and pyrosequencing of a virus isolated from a specimen collected on July 14 had the H275Y mutation, confirming oseltamivir resistance.

The above comments are from today's MMWR dispatch describing two immune-suppressed patients, who represent the first two confirmed cases of oseltamivir resistance in H1N1 pandemic swine flu in the United States. Both patients were from King County in Washington State and initial isolates from both patients were sensitive. In one patient, virus with H274Y was first detected in a sample collected 10 days after the start of treatment, while in the other patient, resistance was detected in a sample collected 18 days after the start of treatment. Because these patients were symptomatic at the start of treatment, the date of detectable resistance is unknown, in contrast to earlier patients who were asymptomatic at the start of prophylactic treatment and became symptomatic 5-6 days later. In the patients treated prophylatically, the appearance of symptoms in the short time frame after the start of treatment suggests the resistant virus was present as a minor population, and the treatment led to detection.

In the two immune-suppressed patients it is harder to draw a conclusion because of the longer time period between the start of treatment and confirmation of resistance. However, the report of two patients from the same area, who began treatment in June, raises concerns that H1N1 with H274Y is silently circulating. In patients who are not immune-compromised, virus is usually cleared with or without Tamiflu treatment and therefore minor populations with H274Y would go undetected. In immuno-compromised patients, as well as those who are on prophylactic Tamiflu, detections of resistance is more common because of the development of symptoms in patients who were previously asymptomatic, or in patients treated with Tamiflu over and extended time frame.

The report on these two patients follow reports of resistance in Hong Kong this week, as well as Singapore, China, and Thailand last week, in addition to media reports last week of resistance in patients in Texas at widely separated locations along the Mexican border, as well as comments from WHO on reports of resistance in an undisclosed number of patients at undisclosed locations.

These continuing reports of resistance at the same genetic position, H274Y, continue to increase concern of widespread resistance silently circulating as a minor population which is not discovered until patients are treated with oseltamivir.

.

[HenryN]

Two more Tamiflu-resistant A/H1N1 cases reported in U.S.

www.chinaview.cn 2009-08-15 10:34:38

Print

HOUSTON, Aug. 14 (Xinhua) -- The Seattle health department said on Friday that two immuno suppressed patients being treated for A/H1N1 flu had been identified as resistant to Tamiflu. One case involved a male teenager with leukemia who received a stem cell transplant in early May, according to local health experts. While recovering in hospital in a single room he contracted A/H1N1 flu, they said, adding the boy has recovered. The second case involved a woman in her 40s, who also has leukemia and had a stem cell transplant late last year, the health experts said. That woman remains in hospital and is being treated with an intravenous form of the only other flu drug available, Relenza, and another antiviral drug, ribavirin, they disclosed, saying the two patients have no links to each other. Local health officials also said that there is no evidence indicating that people who came in contact with the two patients became infected with a Tamiflu-resistant virus. Since the pandemic began, 11 cases of Tamiflu resistance have been reported. Three of those were reported Friday -- the two in Seattle and a new case in Hong Kong. Japan and China have each reported three. In the case of China, one case occurred in Hunan province on the mainland and two in Hong Kong. Canada, Denmark and Singapore have each found one. Most of these cases have occurred in people who took the drug as treatment for the flu or to prevent infection with the flu. The sole exception so far is the case of the California teenager who traveled to Hong Kong. She had not previously taken Tamiflu, suggesting she was infected from the start with a resistant virus. The source of her infection was not found and no other cases of resistance have been reported from the San Francisco area, where she lives. "Viruses can develop drug resistance over time. It's important that antiviral treatments only be used as recommended by a health care provider, to minimize drug resistance and preserve an important tool against the illness for those who need it," said Dr. David Fleming, Director and Health Officer for Public Health of Seattle & King County. "The vast majority of people with H1N1 virus continue to be treatable with Tamiflu, and in cases where it becomes ineffective, other options are available," Dr. Fleming said.

http://news.xinhuanet.com/english/20...t_11885605.htm

[wotan]

To my knowledge none of the other instances of Tamiflu resistance have been in people with immune system problems, but it seems very likely that segment of the population has received a fair amount of Tamiflu. Really, what is the likelihood that two people in the same county developed it spontaneously?

[HenryN]

Originally Posted by wotan

To my knowledge none of the other instances of Tamiflu resistance have been in people with immune system problems, but it seems very likely that segment of the population has received a fair amount of Tamiflu. Really, what is the likelihood that two people in the same county developed it spontaneously?

As the frequency of detection / reporting increases, the likelihood that these acquistions are due to random mutations becomes increasingly remote. The best data for the silent spread actually is the Singapore patient, which was said to be sensitive in the initial test, which was on May 28. The resistance was on a May 30 sample, too soon for "spontaneous" generation.
H274Y is clearly spreading silently, and detection rates will increase (which will be very clear very soon, unless the data is withheld, as was announced by WHO earlier this week).

[mixin]

Originally Posted by niman

No. Its nonsense. Acquiring H and N from human wouldn't create a pandemic strain.

I don't understand your reply. Where was it said that the acquisition would create a new pandemic strain?

[HenryN]

Originally Posted by mixin

I don't understand your reply. Where was it said that the acquisition would create a new pandemic strain?

If there is no pandemic strain, then the lack of reassortment isn't a "good thing".

[gsgs]

it can acquire NA (and others...) and not HA.

any such reassortment is dangerous since it could change virulence.
e.g. it could acquire PB1 with a functional PB1-F2

reassortment means prolonged evolution. Once it goes loose
the virus may get other ideas how to change

[HenryN]

Originally Posted by gsgs

it can acquire NA (and others...) and not HA.

any such reassortment is dangerous since it could change virulence.
e.g. it could acquire PB1 with a functional PB1-F2

reassortment means prolonged evolution. Once it goes loose
the virus may get other ideas how to change

It "could" do a lot of things. However, swine H1N1 that acquires human N almost always also acquires human H. In Sasketchewan, 2 or 3 farm workers were infected with a triple reassortant that was Tamiflu resistance because the virus had acquired the N1 from Bisbane/59, which had H274Y. However, it also acquired H1 from Brisbane/59, so the resulting virus had a human H1N1 serotype, but a pandemic strain is defined by a new serotype. Brisbane/59 H1N1 is not new (and most humans have immunity by virtue of earlier H1N1 seasonal flu infections and earlier vaccination with Brisbane/59 H1N1).

[gsgs]

> but a pandemic strain is defined by a new serotype.

so we have no pandemic

[gsgs]

usually all sorts of reassortments do happen, there are many examples.
I wouldn't rely on HA and NA going to gether.
They didn't in the 1968 pandemic nor in human/swine H1N2

[HenryN]

Originally Posted by gsgs

it can acquire NA (and others...) and not HA.

Please provide examples of swine isolates with H and N that are not either both human or both swine.

[mixin]

Here's a timeline for when the resistance appeared:

1. On May 31, he developed symptoms. Virus showed susceptibility in samples taken on June 4 but resistance in those taken on June 11, July 14 & 30.

On August 6, pyrosequencing at CDC of viral RNA from a specimen collected on June 4 revealed susceptibility to oseltamivir. However, pyrosequencing of a follow-up specimen collected on July 30 indicated oseltamivir resistance, based on detection of the H275Y mutation

On August 10, CDC received previously collected virus isolates from the patient for pyrosequencing on August 11, which confirmed the previous results. A novel influenza A (H1N1) virus isolate from a specimen collected on May 31 was identified as susceptible to oseltamivir by pyrosequencing at CDC, but viruses isolated from specimens collected on June 11 and July 14 had the H275Y mutation, indicating oseltamivir resistance.

2. June 21, she developed symptoms. Virus showed susceptibility in samples taken on June 21 but resistance in those taken on July 14 & 28.

On August 6, CDC determined that pyrosequencing of viral RNA from the first clinical specimen collected on June 21 did not detect the H275Y mutation. However, the mutation was detected by pyrosequencing of viral RNA from a nasal wash specimen collected on July 28. Treatment of the patient with oseltamivir was discontinued when results became available.

On August 10, CDC received other previously collected virus isolates from this patient for testing, and pyrosequencing of a virus isolated from a specimen collected on July 14 had the H275Y mutation, confirming oseltamivir resistance.

[HenryN]

Originally Posted by gsgs

usually all sorts of reassortments do happen, there are many examples.
I wouldn't rely on HA and NA going to gether.
They didn't in the 1968 pandemic nor in human/swine H1N2

The H1N2 in human or swine H1N2 are both human. 1968 didn't involve swine genes.

[HenryN]

Originally Posted by gsgs

> but a pandemic strain is defined by a new serotype.

so we have no pandemic

Swine H1N1 is not human H1N1.

[Mamabird]

Originally Posted by niman

Wrong. The acquiring a Brisbane/59 H and N would produce a strain similar to seasonal H1N1 (population would already have antibodies). Its hopes and dreams on steroid.
It has already happened in Saskatchewan with another triple reassortant.

I take it by this very surprising response that it is your view that the existing Swine Flu cannot reassort with Seasonal Flu to acquire only the NA segment making it Tamiflu resistant.

Otherwise, none of this makes any sense, or you have just misinterpreted the question posed.

Many of us in our responses agree with you on your recombination theory of Tamiflu resistance acquisition, but a reader would not necessarily get that impression by the way you respond to our posts on this forum. You simply say "no" or "wrong" to anything anyone else posts.

[mixin]

I admit to being confused even after Niman explained.

By the little summary I posted, I thought it was clear that the resistance developed "in" both people and was not the result of seasonal combining with panflu (or silent spreading). Considering that a certain percent of people will normally develop a resistance to Tamiflu, I just imagined this was much better than if it had combined.

[gsgs]

****** got HA from swine <1918 and NA from swine which however got it from birds in 1978
mixing of American HA and Eurasian NA in Asia
also:
http://www.cdc.gov/ncidod/eid/vol12no05/05-1060.htm
separation of HA and NA is also assumed to have happened in 1918

swine H1N2 predates human H1N2 e.g. A/swine/Ehime/1/1980(H1N2)

swinish flu may "pick up" NA from humans while keeping its own HA